The debate over precision genome engineering
by Dr. David L. (“Woody”) Woodland
(as published in the Summit Daily News of May 31, 2015)
A debate has emerged in the scientific world concerning genome engineering. Recently, there
have been amazing advances in scientists’ ability to modify genetic material. It is now possible to
manipulate the human genome with extreme precision using new engineering techniques.
Individual genes can be removed and replaced with a different version, or specific mutations can
be corrected, while avoiding damage to unrelated parts of the genome. The technique has opened
up opportunities for gene therapies to repair malfunctioning genes and control infectious agents
such as the human immunodeficiency virus that causes AIDS. But it can also be applied to human
embryos, opening up the potential of correcting mutated genes that cause inherited diseases by
changing an embryo’s DNA before implantation in the womb. At the same time, it could be used by
fertility doctors to add desirable traits to the embryo, producing “designer babies.” Not surprisingly,
these advances have raised alarms among scientists, bioethicists, and the public at large.
Simpler technologies to manipulate genetic material have been around for many years. DNA is
comprised of long strands of molecules called nucleotides that come in four flavors: A, T, G, and C.
Traditional genetic engineering approaches involve cutting and pasting these strands to create new
sequences. The basic approach involves so-called “restriction enzymes” that are able to recognize
specific sequences and cut the DNA at that point. For example, the enzyme EcoR1 cuts DNA at
the sequence “GAATTC.” Other enzymes can paste DNA fragments back together. Restriction
enzymes come in many types with many different sequence specificities and have been a
mainstay of genetic engineering for decades. However, these enzymes lack the precision to
engineer the human genome because they interact with sequences of only 1 to 10 nucleotides that
occur more or less randomly throughout the genome.
In recent years, several advances in our ability to manipulate and engineer DNA have
revolutionized the field. These new approaches involve the creation of artificial restriction enzymes
engineered to cut DNA at any desired sequence. One such technology, referred to as CRISPRs,
takes advantage of a mechanism that bacteria use to protect themselves against viruses. Bacteria
produce structures (CRISPRs) able to kill invading viruses by capturing sequences of genetic
material from the virus and using them as a template to recognize and cut viral genetic material.
The damage to the viral genetic material prevents the virus from replicating and thereby protects
the bacterium. Scientists have commandeered this mechanism by introducing synthetic sequences
of genetic material that direct the cutting of DNA at a desired sequence. The ability to control the
sequence to be cut allows genetic engineers to manipulate DNA with a precision previously
unimaginable and with the potential for both good and evil purposes.
The debate erupted into public view after 18 leading scientists wrote an open letter calling for
regulation of this technology. The letter, entitled “A prudent path forward for genomic engineering
and germline gene modification” discusses “the scientific, medical, legal, and ethical implications of
these new prospects for genome biology.” The authors specifically want to discourage the
technology’s use for engineering human germline cells to generate human embryos. Their central
concerns are for “unknown risks to human health and well-being.” Obviously, such studies pose
important ethical questions, so there needs to be a thorough airing of the ethics involved.
Let’s hope the scientific community can come to a sensible consensus on the use of this powerful
technology. The matter has become even more urgent with two recent developments. First,
researchers have now modified CRISPRs such that they are able to turn genes on and off. In this
case, CRISPRs are targeted directly to the genes’ on/off switch. Second, researchers have
reengineered the CRISPR mechanism four-fold smaller so it can more easily enter cells. This
makes the technology more usable as a drug to treat certain genetic diseases. And third, the
CRISP mechanism has been modified to target RNA molecules that translate messages from the
DNA into proteins, enabling researchers to modify protein production in the cell. These exciting
advances are occurring at breakneck speed and will require constant vigilance by all of us.
David L. “Woody” Woodland, Ph.D. is the Chief Scientific Officer of Silverthorne-based Keystone Symposia
on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening
internationally renowned research conferences in Summit County and worldwide. Woody can be reached at
970-262-1230 ext. 131 or woody@keystonesymposia.org.
For more (Petri) Dish columns, visit www.keystonesymposia.org.